A study of navitoclax and ruxolitinib for myelofibrosis

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Myelofibrosis

Status:

Closed

Phase:

Phase 2

This study is for people who have had at least 12 weeks of ruxolitinib for myelofibrosis but it isn’t working.

Myelofibrosis is a rare blood disorder. It causes scarring of the bone marrow so it can’t make blood cells properly.

Myelofibrosis can develop without having had any other condition. This is called primary myelofibrosis. It can also develop in people who have polycythaemia vera or thrombocythaemia. This is called secondary myelofibrosis. This study is for people with either primary or secondary myelofibrosis.

More about this trial

There are a number of different treatments for myelofibrosis. These might include chemotherapy or targeted drugs such as ruxolitinib.

You usually have ruxolitinib if you develop myelofibrosis symptoms such as an enlarged spleen. But it doesn’t always work or it stops working. So, researchers are looking at having it alongside another drug called navitoclax. They want to see if this can improve response to treatment.

Navitoclax blocks the functions of a protein found in myelofibrosis cells. This causes these cells to die.

There is some early research suggesting that having the 2 drugs together might help people with myelofibrosis. This is the first time people with myelofibrosis will take both drugs together.

The aims of this study are to:

see how safe treatment is

see if adding navitoclax to ruxolitinib improves treatment

learn more about the side effects and quality of life

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.

Who can take part
You may be able to join this study if all of the following apply. You:

have primary or secondary myelofibrosis

have had at least 12 weeks of ruxolitinib at a dose of 10mg or more

have an enlarged spleen that your doctor can feel when they examine you

have satisfactory blood test results

aren’t suitable for a stem cell transplant or you don’t want to have one

are willing to use reliable contraception for 30 days after the last dose of navitoclax if there is any chance you or your partner could become pregnant

are at least 18 years old

Who can’t take part
You cannot join this study if any of these apply.

Myelofibrosis or cancer related
You:

have had radiotherapy to your spleen in the last 6 months

have had surgery to remove your spleen

have myelofibrosis that is changing to acute leukaemia

have taken targeted drugs such as navitoclax or venetoclax previously

have had any other cancer in the last 2 years apart from carcinoma insitu of the cervix, early prostate or non melanoma skin cancer that was successfully treated

are having an experimental treatment as part of another clinical trial

Medical conditions
You:

are taking warfarin or similar drugs that change how your blood clots, apart from low dose aspirin and low molecular weight heparin

have HIV

have an active hepatitis B or hepatitis C infection that needs treatment

have any other serious infection that needs treatment

take medication that affects body substances called CYP enzymes and you had this within 14 days of starting study treatment

have any other serious medical condition or mental health problem that the study team think could affect you taking part

Other
You:

have had grapefruit, Seville oranges or star fruit within 3 days of starting study treatment

are pregnant or breastfeeding

Trial design

This is a phase 2 study. The study team hope about 34 people will take part in the study including 10 people from the UK.

Everyone has ruxolitinib and navitoclax.

Ruxolitinib is a tablet. You take it twice a day, every day.

Navitoclax is a tablet. You take it once a day, every day. You will start on a low dose which the doctors will increase at the earliest every 7 days. When they find the best, highest dose you can have, you continue to have this for the rest of the study. Your doctor might reduce the dose, if required, due to side effects.

You have treatment for as long as it is working and the side effects aren’t too bad.

Samples for research
The researchers will ask to take samples of your bone marrow when you have a bone marrow test. They will also ask to take extra blood tests as part of this study. The researchers plan to:

find out what happens to navitoclax in the body (pharmacokinetics)

look for biomarkers to find out who benefits most from treatment

find out more about myelofibrosis

They will also ask you to take part in a pharmacogenetics research project. You don’t have to take part in this if you don’t want to. You can still take part in the study.

Quality of life
The study team will ask you to fill out a questionnaire before you start treatment and at set times during treatment. The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

You’ll see a doctor and have some tests before you start treatment. The tests include:

At each visit, you see the doctor for a check and blood tests. You have a bone marrow test and MRI every 3 months.

You stop treatment if your myelofibrosis gets worse. You see the study team a month later for a check up. Your doctor will discuss other treatment options with you.

You see the study doctor every 3 months for a check up and an MRI scan if you stopped treatment but your myelofibrosis hasn’t got worse. You continue with these visits until your myelofibrosis gets worse or you start another treatment.

The study team follow you up for 5 years. They might see you at a routine hospital appointment, phone you, or check your medical notes to see how you are getting on.

Side effects

Having navitoclax and ruxolitinib is a new treatment. So, there might be some side effects we don’t know about yet. The study team will monitor you during the time you have treatment and you’ll have a number to call if you are worried about anything.

The most common side effects of navitoclax are:

a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness

The following side effects may happen with ruxolitinib and are very common (may affect more than 10 in 100 people). They include:

a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness

bleeding

bruising

dizziness

headache

tummy (abdominal pain)

diarrhoea

feeling tired (fatigue)

itching

difficulty breathing

muscle spasms

urinary tract infections

weight gain

high cholesterol

high levels of liver enzymes in the blood

high levels of a certain type of fat called triglycerides in the blood

Both navitoclax and ruxolitinib can lower the number of platelets in your blood. You should notify your doctor if you have any bleeding or bruising. You have regular blood tests so the doctor can check your platelets.

Recruitment start:

23/10/2017

Recruitment end:

10/04/2019

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

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